Is CTPS2 p.Pro211Leu (c.632C>T) pathogenic?

CTPS2 p.Pro211Leu (c.632C>T) is classified Uncertain significance in CTPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely pathogenic (0.8438); Absent from gnomAD v4.1.

How common is CTPS2 p.Pro211Leu (c.632C>T) in the general population?

CTPS2 p.Pro211Leu (c.632C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTPS2 p.Pro211Leu (c.632C>T)?

AlphaMissense predicts likely pathogenic (score 0.8438) — an in-silico prediction, not a clinical call.

CTPS2 p.Pro211Leu

c.632C>T · rs2518674822 · VCV2533899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8438	likely pathogenic
REVEL	0.599	indeterminate
SaProt	LLR -14.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 112 kb · p 2.2e-14 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTPS2
Protein: p.Pro211Leu
Coding: c.632C>T
MANE Select: NM_175859
dbSNP: rs2518674822
Type: single nucleotide variant
Location: chrX:16693148 (GRCh38)
Structure: AlphaFold pLDDT 91.79 · 8 PDB

Full CTPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTPS2 p.Gly542= Benign ★★ same type
CTPS2 p.Ala315Thr Conflicting classifications of pathogenicity ★ ⚠ same type
CTPS2 p.Ala428Val Uncertain significance ★ ⚠ same type
CTPS2 p.Ala546Thr Uncertain significance ★ ⚠ same type
CTPS2 p.Arg202Cys Uncertain significance ★ ⚠ same type
CTPS2 p.Arg217Gln Uncertain significance ★ ⚠ same type
CTPS2 p.Arg481Gln Uncertain significance ★ ⚠ same type
CTPS2 p.Arg481Trp Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctps2-p-pro211leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown